1. Field of the Invention
The present invention relates to a modified allergen, which is obtained by altering a major allergen (Der f II) of house dust mites by gene engineering, and to a method for production of the modified allergen. The modified allergen obtained by the production method can be utilized as a medicine for treating allergic diseases.
2. Description of the Related Art
It is considered that many allergic diseases are due to several kinds of symptoms which are developed by sensitization to the antigen causing the diseases, in which an IgE antibody specific for an allergen in blood serum and tissue is produced, and when the antibody is exposed again to the antigen, the antibody reacts with the antigen in each tissue. Particularly, an immediate type reaction is caused by the combination of antigens with IgE antibodies on mast cells and basophils followed by cross-linking the IgE antibodies, and the subsequent release of several kinds of chemical mediators from mast cells or basophils.
There is a method for controlling the binding between the antigen and the IgE antibody as a method for treating allergic diseases. If the binding between the antigen and the IgE antibody is controlled, the cross-linking among the IgE antibodies on mast cells or basophils, and the release of chemical mediators are controlled to have an effect on the treatment.
On the other hand, it appears that allergic diseases, such as bronchial asthma, childhood asthma, atopic dermatitis and the like, are mainly caused by an allergen from mites living in house dust. Several kinds of proteins of major mite allergens have been identified as major mite allergens (Platts-Mills et al., J. Allergy Clin. Immunol., 80, 755; 1987). Furthermore, a method for mass producing a purified major mite allergen has been disclosed (Yuuki et al., Japanese J. Allergology, 39, 557 (1990) and Japanese Patent Application No. 3-254683). In addition, the allergen in which a part of the above purified major mite allergen is changed, and a production method thereof has been filed (Japanese Patent Application No. 5-139793).
However, the proteins of the major allergens of mites which have been reported and identified show problems of an allergic reaction, namely anaphylactic shock, in hyposensitization therapy, because the activity of these allergens is high.
On the other hand, if the modified major mite allergen, which has lower IgE-binding activity or lower allergen activity than wild-type allergens and inhibits the binding of the antigen (Der f II) and the IgE antibody, is obtained, it is possible to provide an effective medicine for treating allergic diseases. The medicine does not show the anaphylactic shock of an allergic reaction caused by antigen administration, and it does not have an effect on the other parts of the immune system since the medicine is specific to the antigen. Modified major mite allergens have been disclosed in Japanese Patent Application Nos. 5-139793 and 5-275897. In the former application, there are problems of maintenance and stability of immunogenicity because the molecular structure is greatly changed by amino acid substitutions. In the latter application, it is not enough to minimize the structural change and to lower the allergen activity because a modified position of the allergen is not satisfactorily specified, and only alanine is used as a substitute amino acid.